Immediate early response gene 3 (IER3) encodes a protein involved in the regulation of apoptosis and differentiation. Recently the role of IER3 in the regulation of extracellular signal-regulated kinases (ERKs) was discovered. IER3 prolongs ERKs activation by inhibition of phosphatase PP2A. Here we show that interleukin-1β (IL-1β)-induced IER3 expression is mediated by the ERK1/2 target, transcription factor Elk-1. We identified sequences in the IER3 promoter responsible for its ERKs-dependent activation, namely ETS5/6. Elk-1 binds to these sequences and is phosphorylated following IL-1β stimulation. Mutation of ETS5/6 binding site abolishes activation of IER3 promoter by IL-1β as well as by the constitutively active form of Elk-1 (Elk-VP16). Thus IER3 acts not only as a regulator of ERKs activation, but also as a ERKs-Elk-1-dependent downstream effector.